U.S. patent number 6,503,953 [Application Number 09/916,962] was granted by the patent office on 2003-01-07 for methods for treating atopic disorders.
This patent grant is currently assigned to Atopic Pty Ltd.. Invention is credited to John K. Vyden.
United States Patent |
6,503,953 |
Vyden |
January 7, 2003 |
Methods for treating atopic disorders
Abstract
A method for treating an atopic disorder in a patient is
provided. The method comprises administering to the patient an
effective amount of at least one of an antifungal and an antibiotic
over a period of time. The method further comprises reducing over
the period of time the application of emollients to the patient by
at least about 50%, relative to the amount of application of
emollients prior to treatment.
Inventors: |
Vyden; John K. (Beverly Hills,
CA) |
Assignee: |
Atopic Pty Ltd. (Sydney,
AU)
|
Family
ID: |
22825545 |
Appl.
No.: |
09/916,962 |
Filed: |
July 26, 2001 |
Current U.S.
Class: |
514/741;
514/826 |
Current CPC
Class: |
A61K
31/13 (20130101); A61K 31/135 (20130101); A61K
31/27 (20130101); A61K 31/4178 (20130101); A61K
31/4196 (20130101); A61K 31/496 (20130101); A61K
31/13 (20130101); A61K 31/135 (20130101); A61K
31/27 (20130101); A61K 2300/00 (20130101); A61K
2300/00 (20130101); A61K 2300/00 (20130101); Y10S
514/826 (20130101) |
Current International
Class: |
A61K
31/135 (20060101); A61K 31/13 (20060101); A61K
31/27 (20060101); A61K 31/21 (20060101); A61K
31/4178 (20060101); A61K 31/4196 (20060101); A61K
31/4164 (20060101); A61K 31/496 (20060101); A61K
031/04 () |
Field of
Search: |
;514/741,826 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Database: Google.com., "Hand Eczema", Novartis Pharmaceuticals
Corp. 1998 National Eczema Association for Science and Education,
total 5 pages, see especially p. 3/5.* .
Database: Google.com., "Atopic Dermatitis: A review of Diagnosis
and Treatment", Correale et al., Sep. 15, 1999. 10 pages.* .
Database Caplus, AN:1987:201534, Okamoto et al., "Percitaneous
absorption and skin sensitization", abstract, 1986, vol. 12, pp.
159-168.* .
Database Caplus, AN:1994:2358, Jaskilecki et al., "Barrier
properties of silicone cream in protection against sensitizing . .
. . ", abstract, 1992, vol. 25(4), pp. 383-386..
|
Primary Examiner: Henley; Ray
Assistant Examiner: Kim; Vickie
Attorney, Agent or Firm: Christie, Parker & Hale,
LLP
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATION
This application claims priority of U.S. Provisional Application
No. 60/220,916, filed Jul. 26, 2000, the entire disclosure of which
is incorporated herein by reference.
Claims
What is claimed is:
1. A method for treating asthma in a patient, comprising:
administering to the patient an effective amount of at least one of
an antifungal and an antibiotic; and reducing the application of
emollients to the patient by at least about 50%, relative to the
amount of application of emollients prior to treatment wherein the
emollients are selected from the group consisting of lotions,
creams, moisturizers, oils, ointments, cocoa butter, greases, skin
softeners, soaps containing lotions or moisturizers, shampoos
containing lotions or moisturizers, sunblocks containing lotions or
moisturizers, cosmetics containing lotions or moisturizers, and
products containing slip.
2. A method according to claim 1, wherein the antifungal is a
fungicidal.
3. A method according to claim 1, wherein the antifungal is
terbinafine.
4. A method according to claim 1, wherein the antifungal is an oral
antifungal.
5. A method according to claim 1, comprising administering both an
antifungal and an antibiotic.
6. A method according to claim 1, wherein the at least one of an
antifungal and an antibiotic is administered over a period of time
of at least about 1 month.
7. A method according to claim 1, wherein the at least one of an
antifungal and an antibiotic is administered over a period of time
of at least about 2 months.
8. A method according to claim 1, wherein the at least one of an
antifungal and an antibiotic is administered over a period of time
of at least about 3 months.
9. A method according to claim 1, wherein the application of
emollients to the patient is reduced by at least about 80%,
relative to the amount of application of emollients prior to
treatment.
10. A method according to claim 1, wherein the application of
emollients to the patient is reduced by at least about 90%,
relative to the amount of application of emollients prior to
treatment.
11. A method according to claim 1, wherein the application of
emollients to the patient is reduced by at least about 95%,
relative to the amount of application of emollients prior to
treatment.
12. A method according to claim 1, wherein the application of
emollients to the patient is ceased.
13. A method according to claim 1, wherein the administration is
over a first period of time of at least about 1 month, and the
reduction is over a second period of time of at least about 6
months.
14. A method according to claim 13, wherein the first period of
time is at least about 3 months.
15. A method according to claim 14, wherein the second period of
time is at least about 1 year.
16. A method according to claim 1, further comprising administering
an antihistamine.
17. A method for treating asthma in a patient, comprising:
administering to the patient an effective amount of an antifungal;
administering to the patient an effective amount of an antibiotic;
and reducing the application of emollients to the patient by at
least about 80%, relative to the amount of application of
emollients prior to treatment, wherein the emollients are selected
from the group consisting of lotions, creams, moisturizers, oils,
ointments, cocoa butter, greases, skin softeners, soaps containing
lotions or moisturizers, shampoos containing lotions or
moisturizers, sunblocks containing lotions or moisturizers,
cosmetics containing lotions or moisturizers, and products
containing slip.
18. A method according to claim 17, wherein the antifungal is
administered over a period of time of at least about 2 months.
19. A method according to claim 17, wherein the antifungal is
administered over a period of time of at least about 3 months.
20. A method according to claim 17, wherein the antibiotic is
administered over a period of time of at least about 2 months.
21. A method according to claim 17, wherein the antibiotic is
administered over a period of time of at least about 3 months.
22. A method according to claim 17, wherein the third period of
time is at least about 3 months.
23. A method according to claim 17, wherein the third period of
time is at least about 6 months.
24. A method according to claim 17, wherein the reduction of
emollients occurs simultaneously with at least part of the period
of time over which the antifungal is administered.
25. A method according to claim 17, wherein the antifungal is a
fungicidal.
26. A method according to claim 17, wherein the antifungal is
terbinofine.
27. A method according to claim 17, wherein the application of
emollients to the patient is reduced by at least about 95%,
relative to the amount of application of emollients prior to
treatment.
28. A method according to claim 17, wherein the application of
emollients to the patient is ceased.
29. A method according to claim 17, further comprising
administering an antihistamine.
30. A method according to claim 29, wherein the administration of
the antihistamine is provided over a period that overlaps, at least
in part, with the administration of the antibiotic.
31. A method for treating asthma in a patient, comprising:
administering to the patient an effective amount of at least one of
an antifungal and an antibiotic; and simultaneously reducing the
application of emollients to the patient by at least about 50%,
relative to the amount of application of emollients prior to
treatment, wherein the emollients are selected from the group
consisting of lotions, creams, moisturizers, oils, ointments, cocoa
butter, greases, skin softeners, soaps containing lotions or
moisturizers, shampoos containing lotions or moisturizers,
sunblocks containing lotions or moisturizers, cosmetics containing
lotions or moisturizers, and products containing slip.
32. A method according to claim 31, comprising administering both
an antifungal and an antibiotic.
33. A method according to claim 32, wherein the antifungal is a
fungicidal.
34. A method according to claim 32, wherein the antifungal is
terbinafine.
35. A method according to claim 32, wherein the antifungal and
antibiotic are administered over a period of time of at least about
1 month.
36. A method according to claim 32, wherein the antifungal and
antibiotic are administered over a period of time of at least about
2 months.
37. A method according to claim 32, wherein the antifungal and
antibiotic are administered over a period of time of at least about
3 months.
38. A method according to claim 31, wherein the application of
emollients to the patient is reduced by at least about 80%,
relative to the amount of application of emollients prior to
treatment.
39. A method according to claim 31, wherein the application of
emollients to the patient is ceased.
40. A method according to claim 31, further comprising
administering an antihistamine.
41. A method according to claim 6, wherein the application of
emollients is reduced over a period of time of at least about 1
month.
42. A method according to claim 7, wherein the application of
emollients is reduced over a period or time of at least about 2
months.
43. A method according to claim 8, wherein the application of
emollients is reduced over a period of time of at least about 3
months.
44. A method according to claim 17, wherein: the antifungal is
administered over a period of time of at least about 1 month; the
antibiotic is administered over a period of time of at least about
1 month; and the application of emollients is reduced over a period
of time of at least about 1 month.
45. A method according to claim 17, wherein: the antifungal is
administered over a period of time of at least about 2 months; the
antibiotic is administered over a period of time of at least about
2 months; and the application of emollients is reduced over a
period of time of at least about 2 months.
46. A method according to claim 17, wherein; the antifungal is
administered over a period of time of at least about 3 months; the
antibiotic is administered over a period of time of at least about
3 months; and the application of emollients is reduced over a
period of time of at least about 3 months.
Description
FIELD OF THE INVENTION
The present invention is directed to methods for treating atopic
disorders, including asthma, eczema, sinusitis, bronchitis, and
allergic rhinitis.
BACKGROUND
In the United States and other Western countries, the reported
incidence of asthma is about 4-5% of the population. About half the
cases develop before the age of ten and another third before the
age of forty. The cost of treating asthma is enormous. Emergency
room visits approximate two million a year and hospitalizations,
about 500,000. Total cost of medication is estimated at one billion
dollars a year, while the loss of productivity within the families
of children is perhaps another billion dollars a year. The number
of asthma prescriptions is thought to double per decade. In the
United Kingdom, the cost of asthma treatment represented 11% of the
national health budget.
The physiological hallmark of asthma is a reversible obstruction in
the airways brought about by vascular congestion, thick tenacious
secretions, bronchial wall edema, and smooth muscle contractions.
During an attack, there is a compromise of lung function. Asthma is
a chronic inflammatory disease of uncertain cause. A noticeable
therapeutic change is the increased use of corticosteroids in its
management.
The United Kingdom has one of the highest rates of asthma per
capita of anywhere in the world. The jet stream flowing across the
Atlantic keeps the British Isles wet, damp, and humid. They have an
advanced "westernized" society and since dampness makes mildew
grow, one sees a high incidence of asthma.
The United States, also a "western" society, has diversified
weather due to its greater size. For instance, a large part of the
western United States is desert. Denver and Arizona have two of the
lowest areas of humidity and asthma. Asthmatics frequently move to
these areas, particularly Arizona, because the extreme heat and low
humidity dry dampness kill mildew and improve asthma.
In Sweden, high indoor humidity is associated with increased
asthma. (See Aberg N. Asthma and Allergic rhinitis in Swedish
conscripts. Clin Exp Allergy 1989;19:59-63; and Wickman M, Nordvall
S L, Pershagen G. Risk factors in early childhood for sensitization
to airborne allergens. Pediatr Allergy Immunol 1992;3:128-33.)
Increases in asthma and allergic diseases are related to an
increasingly unventilated environment. (See Aberg N, Hesselmar B,
Aberg B, Eriksson B. Increase of asthma, allergic rhinitis and
eczema in Swedish school children between 1979 and 1991. Clin and
Experimental Allergy 1995;25:815-819.) High indoor humidity and
houses damaged by dampness, owing to poor ventilation, are related
to a high frequency of allergic symptoms. (See Andrae S, Axelson O,
Bjorksten B, Frediksson M, Kjellman -IM. Symptoms of bronchial
hyperreactvity and asthma in relation to environmental factors.
Arch Dis Child 1988;63:473-8.) Environmental exposure early in life
also seems important. (See Bjorksten B. Risk factors in early
childhood for the development of atopic diseases. Allergy
1994;49:400-7; and Aberg N. Birth season variation in asthma and
allergic rhinitis. Clin Exp Allergy 1989;19:643-8.) Dampness in
homes expressed as moisture inside windowpanes, and as a noticeable
dampness or mildew in the home, increased the risk of asthma,
rhinitis and eczema, as well as a history of upper respiratory
infections. There is a dose response relationship between the
amount of moisture inside the Windows and risk. The highest risk
from dampness exposure is in the first year of life.
A risk factor in allergic diseases is a parental history of
allergic disease. About twice as many children have allergic
disease if one parent was ever afflicted, and three times as many
if both parents were afflicted, as compared with cases with no
parental history (p<0.001). If parents smoked during the first
year of life, it did not increase the risk for development of an
allergic disease, not even asthma of the worst severity. The
frequency of upper respiratory infections and dampness in the homes
were additive, but not synergistic.
Some researchers suggested that indoor air quality and factors of a
chemical or microbiological nature related to damp homes are
important to the pathogenesis of allergic disease. (See Aberg N,
Sundell J, Eriksson B, Hesselmar B, Aberg B. Prevalence of allergic
diseases in school children in relation to family history, upper
respiratory infections and residential characteristics. Allergy
1996;51 :232-237.) They also found that high indoor air humidity
and dampness were strong risk factors underlying all allergic
disease. Inhaled fungus seems able to cause further sensitization
with resultant symptoms. High indoor air humidity and dampness
might encourage fungus growth on skin and in the upper or lower
respiratory tracts. He also found that recent repainting and
repairing of a child's bedroom moderately increased risk of
allergic disease. Repairing and repainting of bedroom walls are
notorious for exposing underlying dampness and mildew and releasing
it into the bedroom environment. Finnish workers reported evidence
between, and association with, mold or mildew problems in school
buildings and the presence of manifest and occult asthma in the
pupils. (See Taskinen T, Meklin T, Nousiainen M, Husman, T,
Nevalainen A, Korppi M. Moisture and mold problems in schools and
respiratory manifestations in school children: clinical and skin
test findings. Acta Paediatr 1997;86:1181-7.)
Yemaneberhan, et al., working in Ethiopia, believe that the asthma
and allergy being seen in developing countries may be associated
with the adoption of a "western" lifestyle. (See Yemaneberhan H,
Bekele Z, Venn A, Lewis S, Parry E, Britton J. Prevalence of wheeze
and asthma and relation to atopy in urban and rural Ethiopia. The
Lancet 1997;350:85-90.) This group found that wheeze and asthma are
especially rare in the rural subsistence areas of Ethiopia where
there is a reduced prevalence of these symptoms in this
environment. In Jimma, which is partly westernized, self-reported
asthma emerged as a clinical problem about ten years before their
studies began, which is consistent with an effect of new
environmental exposures. Although they could not identify the
factor leading to increases in asthma and allergy, general changes
in the domestic environment are likely to be involved.
Furthermore, Esamai and Anabwani found in Kenya that the prevalence
of wheezing, rhinitis, and itchy rashes were similar to previous
studies in Estonia. (See Esamai F, Anabwani G M. Prevalence of
asthma, allergic rhinitis and dermatitis in primary school children
in Uasin Gishu district, Kenya. East Afr Med J 1996;73(7):474-478.)
The prevalence of asthma and allergic diseases are increasing
worldwide, and it is more so in developing countries, which rapidly
raise the living standard of parts of their population.
Trepka et al. studied the epidemiology of asthma, rhinitis and
atopic dermatitis in Eastern versus Western populations. They found
that the rate of physician diagnosed asthma and rhinitis were
higher in Western Germany, though there was a tendency for slightly
less atopic dermatitis in children. They speculated that if
lifestyle and environmental factors play a role in this process,
then the incidence of disease should converge, as the two societies
become more similar. (See Trepka M J, Heinrich J, Wichmann H E. The
epidemiology of atopic diseases in Germany: an east-west
comparison. Rev Environmental Health 1996;11(3): 119-31.)
Hong Kong studies suggest that genetic and/or environmental factors
common to the families are more important than auto aeroallergen
sensitization in the pathogenesis in asthma and allergy in
"westernized" Asia. (See Lau Y L, Karlberg J, Yeung C Y. Prevalence
of and factors associated with childhood asthma in Hong Kong. Acta
Paediatrica 1995;84(7): 820-2.) In Istanbul, atopic family history,
food allergy, eczema, frequent otitis media, and sinus attacks were
found to be of significance in asthma's presence (22). When 1,500
lung experts met in Bangkok, Thailand, on Nov. 25, 1998, they
agreed that the breath-robbing disease is on the rise in many
countries, especially among children, and that a westernized life
style was a major risk factor.
The International Study of Asthma in Childhood (ISAAC) studied
463,801 children, aged 13 to 14 years, situated in 155
collaborating centers in 56 countries. (See Lewis, S. ISAAC--a
hypothesis generator for asthma? The Lancet 1998;351:1220-1224;
Asher M I, Keil U, Anderson H R, Beasley R, Crane J, Mrtinez F,
Mitchell E A, Pearce N, Sibbald B, Stewart A W, Strachan D, Weiland
S K, Williams H C. International study of asthma and allergies in
childhood (ISAAC): rationale and methods. Eur Respir J 1995;
8:483-491; and Writing Group and Steering Committee. Worldwide
variation in prevalence of symptoms of asthma, allergic
rhinoconjunctivitis, and atopic eczema: ISAAC. The Lancet
1998;351:1225-32.) One finding of the study was that countries with
the lowest asthma rates, including several Eastern European
countries, Indonesia, Greece, China, Taiwan, Uzbekistan, India, and
Ethiopia, also had the lowest prevalence of allergic conjunctive,
rhinitis and atopic eczema.
ISAAC found that the highest prevalence for asthma symptoms was
mainly in English speaking centers and mainly in Western countries.
These findings raised the possibility that environmental factors
relating to living conditions in these countries are important. By
contrast with the asthma findings, the highest prevalence of
allergic rhinitis symptoms were reported from different centers in
the world. Several centers with the highest symptom prevalence were
not represented among the countries with the highest asthma
prevalence. ISACC suggests that the major risk factors for these
related disorders may differ or may involve different latency
periods and time trends.
Allergic rhinitis may be missed in children, if some of the classic
symptoms or signs are missing or they have indolent infections. A
further problem is that "eczema" in one set of countries may be
brushed off as simple "dry skin" in others. Some children may have
been taught to consider so-called "dry skin" as nothing to worry
about, and certainly not eczema. Sociological conditioning in
different cultures as to what is normal or not may play some part
in ISMC's findings.
When self reported symptoms of more than one atopic disorder were
taken in to account, the highest prevalence were again observed in
English speaking, westernized countries. ISMC also found that
remarkable differences, and widely different prevalence, occurred
between centers with populations of similar ethnic origins in
countries such as China, (including Taiwan and Hong Kong), India,
Italy, and Ethiopia. Once again these phenomena may have multiple
causes that could in part be explained by the influence of Western
culture.
Eczema is seen throughout life with an age distribution similar to
that of asthma. Investigators have drawn attention to a seeming,
but not understandable relationship between these two entities.
(See Daniels Se, Bhattacharrya S, James A, Leaves N I, Young A,
Hill M R, Faux J, Ryan G F, Ie Souef P N, Lathrop G M. A
genome-wide search for quantitative trait loci underlying asthma.
Nature. Sep. 19, 1996. 383(6597)L247-50.) In rich "westernized"
countries, both are increasing. Various topical corticosteroids and
antihistamines are commonly used in treatment. As with asthma,
systemic corticosteroids are limited to severe exacerbations.
Usually oral corticosteroids clear the skin only briefly. Stopping
their use usually results in a return of the dermatitis. As with
sinusitis and asthma, systemic corticosteroids bring about
amelioration, but not cure. The use and effects of corticosteroids
in the three diseases is similar.
Sinusitis, like eczema and asthma, is considered an inflammatory
disease, the prevalence of which is rising. Possibly, 14% of the
population is affected. Antibiotics, decongestants, antihistamines,
and surgery are often used in its treatment, while corticosteroids
are used to control it. (See Horner W E, Helbling A, Salvaggio J E,
Lehrer S B. Fungal allergens. Clin Microbiol Rev
1995;8(2):161-179.)
SUMMARY OF THE INVENTION
The present invention is based on the discovery that eczema,
allergic rhinitis and asthma result as a progression of the same
disease process. This illness often first manifests itself as a
fungal disease of the skin, which can become complicated by
bacterial infection (Stage I).
Stage II is the inhalation, infection and sensitization of the
nasal passages by the skin infection setting up an "allergic
rhinitis." As time passes and with only symptomatic treatment, the
mixed infective process increasingly damages the upper airway
system and a chronic sinusitis may occur.
Stage III is a spreading of the infection into the airways &
lungs and its sensitization by the same infective process,
resulting in inflammatory airways obstruction, chronicity and the
development of a myriad of secondary changes in the respiratory
system and body.
More specifically, there are two parts to Stage I of the syndrome.
The skin develops a fungal infection, which is mistakenly called
"dry skin" (Stage IA). In the second part of the first stage this
fungal infection spreads, becomes noticeably infected with
bacteria, and is called "eczema" (Stage IB). The presence of either
can result in the development of allergic rhinitis (Stage II A)
and/or sinusitis (Stage II B).
Mildew, a type of fungi, usually results in situations when a
normally dry surface becomes chronically wet. If a person's skin
becomes chronically wet, the result will be infestation with fungi.
Many experience this between their fourth and fifth toes when they
do not dry off properly on a continual basis. Water normally
evaporates off the skin even when not dried off with a towel.
However, when water collects between the toes where air cannot
reach it well, thereby keeping this area chronically wet, a
condition we call "athlete's foot" or tinea pedis may develop. It
may be mistaken for "dry skin," but it is actually a dermaphytic
fungal infection.
When various substances such as lotions, moisturizers, oils,
ointments, Vaseline, cocoa butter, greases, skin softeners and many
baby care products are put on the skin, they can make the skin wet
for weeks causing mildew to form on it. Most people mistake the
mildew for so-called "dry skin." Soon to be patients see the white,
flaky mildew on their skin, and assume that the skin is "dry." This
results in their applying more lotion, which results in more and
more mildew. Gradually the deposits of mildew become more obvious
in various areas of the body, such as the heels, elbows, kneecaps,
finger-webs, cheeks and scalp. Medically, when skin becomes
chronically wet and infected with fungus, it is called tinea
corporis (tinea of the body), tinea capitis (head), tinea cruris
(groin), tinea manuum (hands), and tinea barbae (face). Once tinea
is established in a body area, it requires treatment with a
systematic antifungal drug, like itraconazole or terbinafine to get
rid of it. If the infection is not treated in its entirety and
completely cured, it tends to reoccur.
Giving cortisone or its derivatives merely treats the symptoms, but
does not cure the infection. As a result, the lesions live on,
causing chronicity and gradual spread over the body, particularly,
if the daily application of lotions and moisturizers continues.
This disease is then called "eczema" (Stage 1B).
The inventor has treated numerous patients with "eczema" and
discovered that a large majority of the patients are cured by the
use of oral antifungals for a period of time and/or antibiotics,
preferably a combination of an antifungal and antibiotic. An oral
antihistamine may be also be administered to help control itch,
particularly in the early weeks of treatment. A part of this
treatment is a cessation of all application of emollients, such as
lotions, moisturizers, and the like. In one embodiment, the
invention is directed to a method for treating eczema comprising
reducing the application of emollients and administering an
antifungal and/or an antibiotic.
Stage II is the development of "allergic rhinitis" (Stage IIA),
which can, overtime, develop into an associated chronic sinusitis
(Stage IIB). Itching of the conjunctiva, nose and pharynx, episodic
rhinorrhea, sneezing, with obstruction of the nasal passages
occurs. An incidence rate of about 7% is seen in North America. It
is most common in childhood and adolescence. Swelling of turbinates
and mucous membranes with obstruction of the sinus ostia and
Eustachian tubes can cause secondary infections of the sinuses and
middle ear. Nasal polyps often arise concurrently with edema and/or
infection within the sinuses and increase obstructive symptoms.
If a person has fungus growing on their upper torso, face and/or
scalp, it is just a matter of time before it would be inhaled into
the nose and upper airways. Since it will be inhaled onto a wet
surface, it is likely to take hold, perhaps causing a primary
infection, a sensitizing reaction or a further sensitization to the
fungus or perhaps all three. What begins as rhinitis can cause
secondary sinusitis.
A useful first step in the treatment of sinusitis is the endoscopic
removal of polyps and inflammatory material to establish aeration
and drainage of involved sinuses, followed by administration of an
antifungal agents along with reduction of application of
emollients.
More specifically, when sinusitis has been present for years, the
inventor has noted that a fungal infection may be part of the
process and can cause "peanut butter" like plugs. Within the
sinuses there are strategic areas such as the meatus in the ethmoid
complex that are narrow. If these become blocked, as happens in
infections, then obstructive sinusitis occurs. A fungus infection
in an already damp environment tends to chronicity, making it easy
to see how a fungal infection could cause obstructive sinusitis,
with its resultant pathology.
These "peanut butter like" plugs should be surgically removed, such
as by camera-controlled laparoscopic sinus surgery. However, for
fungal sinusitis to be properly cured, the further inhalation of
fungus from outside the nasal passages and sinuses must stop,
thereby requiring the reduction of application of emollients.
Additionally, effective control of sinusitis can result in
improvement of asthma.
Stage III is a spreading of the infection into the airways &
lungs and its sensitization by the same infective process,
resulting in "bronchitis"(Stage IIIA) and/or "asthma"(Stage IIIB).
Clinically, chronic bronchitis is often an early part of the onset
of reversible obstructive airways disease. In another embodiment,
the invention is directed to a method of treating bronchitis and/or
asthma. The method comprises administering an antifungal and/or an
antibiotic for a period of time and reducing the administration of
emollients over that period of time.
The methods of the present invention, which involve the reduction
or cessation of the administration of emollients is consistent with
the knowledge that, as the level of income rises and populations
become more "westernized", atopy takes hold. Specifically, as
disposable income increases, the sale of "luxury" items, including
perfumes, shampoos, cosmetics and skin care preparations,
increases. The poor in rural areas and less-developed countries
cannot afford such items. Nor are such people subject to the
propaganda and salesmanship of the cosmetic industry, glossy
magazines, and television. Additionally, the theory of the
invention tends to explain why parental asthma is a risk factor,
since parents who put lotions and the like over their own skin tend
to do it to their children.
In one embodiment, the invention is directed to a method for
treating an atopic disorder in a patient. The method comprises
administering to the patient an effective amount of at least one of
an antifungal and an antibiotic over a period of time. The method
further includes reducing over the period of time the application
of emollients to the patient by at least about 50%, relative to the
amount of application of emollients prior to treatment.
In another embodiment, the invention is directed to a method for
treating asthma comprising administering to the patient an
effective amount of an antifungal over a first period of time and
administering to the patient an effective amount of an antibiotic
over a second period of time. The method further comprises reducing
the application over a third period of time of emollients to the
patient by at least about 80%, relative to the amount of
application of emollients prior to treatment.
DESCRIPTION OF THE DRAWINGS
These and other features of the advantages of the present invention
will be better understood by reference to the following detailed
description when considered in conjunction with the accompanying
photographs wherein:
This application file contains at least one photograph executed in
color. Copies of this patent application publication with color
photographs will be provided upon request and payment of the
necessary fee.
FIG. 1A is a photograph showing Patient A (Example 6) prior to
treatment.
FIG. 1B is a photograph showing Patient A after treatment.
FIG. 2A is a photograph showing Patient B (Example 6) prior to
treatment.
FIG. 2B is a photograph showing Patient B after treatment.
FIG. 3A is a photograph showing Patient C (Example 6) prior to
treatment.
FIG. 3B is a photograph showing Patient C after treatment.
FIG. 4A is a photograph showing Patient D (Example 6) prior to
treatment.
FIG. 4B is a photograph showing Patient D after treatment.
FIG. 5A is a photograph showing Patient E (Example 6) prior to
treatment.
FIG. 5B is a photograph showing Patient E after treatment.
FIG. 6A is a photograph showing Patient F (Example 6) prior to
treatment.
FIG. 6B is a photograph showing Patient F after treatment.
FIG. 7A is a photograph showing Patient G (Example 6) prior to
treatment.
FIG. 7B is a photograph showing Patient G after treatment.
FIG. 8A is a photograph showing Patient H (Example 6) prior to
treatment.
FIG. 8B is a photograph showing Patient H after treatment.
DETAILED DESCRIPTION
In accordance with the methods of the invention, the administration
of emollients is reduced by at least about 50%, more preferably at
least about 80%, still more preferably at least about 90%, even
more preferably at least about 95%, relative to the amount of
application of emollients prior to treatment. In a particularly
preferred embodiment, the administration of emollients is ceased
altogether. As used herein, the term "emollients" includes lotions;
creams; moisturizers; oils; ointments; cocoa butter; greases; skin
softeners; soaps, shampoos, sunblocks, cosmetics and other products
containing lotions, moisturizers or the like; products containing
"slip" (a binder that allows pigment to slide across the skin); and
any other product that softens the skin or soothes irritation in
the skin. The period of time over which the administration of
emollients is reduced or ceased is preferably at least about 1
month, more preferably at least about 2 months, still more
preferably at least about 3 months, even more preferably at least
about 6 months, yet more preferably at least about 1 year. The
reduction or cessation of the administration of emollients is
preferably continued for as long as possible to minimize the
possible recurrence of the atopic disorder.
Suitable antifungals for use in connection with the invention
include griseofulvin (such as FULVICIN, commercially available from
Schering Corporation, Kenilworth, N.J.); ketoconazole (such as
NIZORAL tables, commercially available from Janssen Pharmaceutica
Inc., Titusville, N.J.); itraconazole (such as SPORANOX,
commercially available from Janssen Pharmaceutica Inc.); and
fluconazole (such as DIFLUCAN, commercially available from Pfizer
Inc., New York, N.Y.). Particularly preferred anti-fungals are
fungicidals, such as terbinafine (sold under the name LAMISIL by
Novartis Pharmaceuticals Corporation, East Hanover, N.J.)
naftifine, butemaifine, and amorolifine. The antifungal is
preferably administered over a period of time of at least about 1
month, more preferably at least about 2 months, still more
preferably at least about 3 months. Preferably the antifungal is
administered to the patient in a dose ranging from about 10 mg to
about 2000 mg per day, more preferably from about 250 mg to about
1000 mg per day.
Culture and sensitivity of the underlying lesion should determine
the antibiotic. Suitable antibiotics for use in connection with the
present invention include ciprofloxacin (such as CIPRO,
commercially available from Bayer Corporation, West Haven, Conn.);
trovafloxacin mesylate (such as TROVAN, commercially available from
Pfizer Inc.); clavulanate potassium, amoxicillin and combinations
thereof (such as AUGMENTIN, commercially available from SmithKline
Beechm Pharmaceuticals, Philadelphia, Pa.); levofloxacin (such as
LEVAQUIN, commercially available from Ortho-McNeil Pharmaceuticals,
Raritan, N.J.); cefuroxime (such as CEFIN, commercially available
from Glaxo Wellcome, Research Triangle Park, N.C.); clarithromycin
(such as BIAXIN, commercially available from Abbott Laboratories,
North Chicago, Ill.); tobramycin (such as NEBCIN, commercially
available from Eli Lilly, Indianapolis, Ind.); azithromycin (such
as ZITHROMAX, commercially available from Pfizer, New York, N.Y.);
cephalexin; cefixime; cefpodoxime proxetil; flurconazole;
trimethoprim; and sulfamethaxazole. The antibiotic is preferably
administered over a period of time of at least about 1 month, more
preferably at least about 2 months, still more preferably at least
about 3 months. If both an antifungal and an antibiotic are
administered, the antibiotic is preferably administered over a
period of time concurrent, at least in part, with the period of
time over which the antifungal is administered. Preferably the
antibiotic is administered to the patient in a dose ranging from
about 10 mg to about 2000 mg per day, more preferably from about
250 mg to about 1000 mg per day.
EXAMPLES
The following examples describe case studies showing the effect of
application of an emollient and the reduction thereof on atopic
disorders.
Example 1
A male, 33 year old patient recalled his mother putting lotion on
his skin every day until the age of ten, at which time he had
terrible asthma. His parents separated and he went to live with his
father. His father put no lotion on him and over a period of time
his asthma disappeared. Now in his 30's, the patient lives with his
girlfriend who insists on putting lotion on his skin at every given
opportunity. He now shows mildew on his elbows and knees and states
that his sinuses are really "playing-up." He is starting to have
asthma attacks once again.
Example 2
A male, 30 year old patient related that his mother put lotion on
him everyday as a child, and he was continually being taken to the
emergency room. At the age of seven or eight, his mother stopped
putting lotions on him and at the age of approximately 14, his
asthma had gone away. When he started dating girls at 17 or 18
years of age, he started putting lotion on his skin again, and has
had asthma ever since.
Example 3
A female, 38 year old patient indicated that her mother and her
aunts all used lotion everyday and all had asthma. She could never
remember a time in her life when her mother did not put lotion on
her skin, a habit which she took over as she got older. She has
four children, three of which she "lotioned-up" daily with great
vigor. These three children developed asthma. The only time she had
a remission at all from her illness was when she was a young
teenager and during her third pregnancy, for reasons she did not
understand. At the time of first consultation, she required four
breathing treatments daily, with one occurring during the night.
Her peak flows were in the range of 80. She was never without
inhalers. She was attracted by the idea of giving up lotion
altogether to save money and see what would happen. This patient
did not take any antibiotics or antifungal medication. Within
weeks, her "ash" was falling off her skin and after six weeks, she
went into her first remission in 14 years. Peak flows went from 80
to 350. She needed no more breathing treatments and rarely used an
inhaler.
Example 4
A male, 30 year old patient had been free of asthma and rhinitis
all of his life, when he started putting lotions on his face on a
daily basis for months. He developed asthma about one year later.
He stopped putting lotion on his face, and his asthma nearly went
away. However, he still had his sinusitis. At rest his peak flow
was 435, but after albuterol and beclomethasone inhalers, it was a
normal 570.
Example 5
A female, 26 year old patient told of suffering from severe
sinusitis and then asthma for months, yet physical examination
showed no signs of tinea corporis. She stated she never put any
lotions, etc. anywhere on her skin. When asked why her hair was so
closely cropped, she related that she developed terrible psoriasis
on her scalp when she switched her hair shampoo 2 years previously.
Examination showed she really suffered from tinea capitis.
Example 6
Eight patients that skin fungal conditions were treated by
administration of griseovulvin (500 mg, twice a day) and an
appropriate antibiotic chosen by the culture and sensitivity. Most
patients received an antihistamine for the first ten days to
control itch. The patients ceased the use of lotions and other
emollients, as well as the use of local and systemic
corticosteroids. The results were impressive, as described
below.
Patient A--As shown in FIG. 1A, Patient A had "dry skin" syndrome
fostered by years of skin care products. FIG. 1B, shows Patient A
after 35 days of treatment. Although some white fungus can still be
observed, the appearance of "dry skin" cleared up considerably.
Patient B--As shown in FIG. 2A, Patient B was covered in fungus,
and Patient B had a bacterial infection. FIG. 2B shows Patient B
one week later, with the fungus having improved dramatically.
Patient C--Patient C had spent almost 24 years visiting
dermatologists in an attempt to clear his skin condition, as shown
in FIG. 3A. Upon culturing the fungus, we discovered it to be
proteus. FIG. 3B shows Patient C after treatment, with the fungus
significantly improved.
Patient D--FIG. 4A shows the fungus on the back of Patient D's
neck. This is believed to be a result of the use of shampoo and
other hair products containing moisturizer. The products ran off
the back of the patient's hair and stayed on his neck, creating a
fungus growth followed by a bacterial infection. FIG. 4B shows
Patient D after seven weeks, with the fungus growth significantly
diminished.
Patient E--Prior to treatment, Patient E, an African American, was
while over almost all of his body. FIG. 5A shows only Patient E's
knee area, although his arms, hands, back, abdomen and neck were
also all while. He also had a very severe case of itching, and he
was put on 100 mg of diphenhydramine four times a day to help
control his itch. FIG. 5B shows Patient E in the sub-patella area
after eleven weeks of treatment. The white skin shown in this
photograph is actually scar tissue from years of scratching.
Patient F--Patient F had a severe fungal conduction, as shown in
FIG. 6A, and had been treated with Lidex for twenty-eight years.
After seven weeks of treatment, the fungas was improving and
peeling off, as shown in FIG. 6B.
Patient G--Patient G, shown in FIG. 7A, had the fungal infection
tinea barbae, but had previously only been treated for acne. FIG.
7B shows Patient G after seven weeks, with the fungal infection
significantly cleared, although scars still remain.
Patient H--Patient H, shown in FIG. 8A, had hair follicles that
became infected byfungus. After nine weeks of treatment, his skin
was dramatically improved, as shown in FIG. 8B.
Example 7
Thirty-two randomly-selected successive asthma patients were
treated by administration of griseovulvin (500 mg, twice a day) and
ciprofloxacin (CIPRO, one double-strength tablet twice a day). All
of the patients ceased use of all lotions and other emollients
during treatment.
For each patient, peak flow measurements were taken using a peak
flow meter, where a higher peak value typically indicates improved
breathing. Counts were taken of eosinophils, which secrete chemical
mediators that can cause bronchoconstriction in asthma. Counts were
also taken of IgE antibodies. The use of an inhaler by each patient
was also monitored.
Patient 1 (age 44) had been on Prednisone until 6 weeks before
treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 240
270 260 1 14 360 1 19 620 0
Patient 2 (age 36)
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 450
2 14 600 0 19 620 0
Patient 3 (age 54) had been on prednisone for many years prior to
treatment and had undergone multiple hospitalizations for her
asthma. During treatment, her dosage of prednisone was slowly
decreased.
Daily Dose of Prednisone Peak IgE Inhaler use Day (mg) Flow
Eosinophils antibodies per day 1 40 370 6-8 13 5 240 5 20 7.5 400 3
26 3.3 380 2 32 2.5 450 1
Patient 4 (age 45)
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 550
322 214 1 8 630 0 15 650 0
Patient 5 (age 23)
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 160
3 4 320 2
Patient 6 (age 63) had been on Prednisone for most of the fifteen
years preceding treatment, had previously been in the intensive
care unit, and had been hospitalized over sixty times for asthma
prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 230
912 530 6 21 450 561 764 4 25 530 179 3 32 750 176 3 43 710 2
Patient 7 (age 50) had been in the intensive care unit four times
for asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 340
256 2 7 440 1 14 500 1
Patient 8 (age 21)
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 455
3 8 540 0
Patient 9 (age 50) had been in the intensive care unit four times
for asthma prior to treatment
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 340
256 65 2 7 440 1 14 500 85 1
Patient 10 (age 21)
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 349
352 3 8 550 1
Patient 11 (age 42) had been in the emergency room three times and
the hospital twice for asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 480
70 140 3 16 430 0
Patient 12 (age 39) had been in the intensive care unit and
hospital prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 180
322 169 2 14 460 0
Patient 13 (age 30) had been in the emergency room five times for
asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 250
246 285 2 21 480 0
Patient 14 (age 58)
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 485
8 30 540 50 580 90 570 110 620 130 635 0 140 620 150 640 170 620
330 650 370 640 0
Patient 15 (age 27) had polydermaphytis and nasal and perioral rash
with green sputum.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 360
432 31 0 9 480 0
Patient 16 (age 67) had forty emergency room visits and ten
hospitalization for asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 250
767 750 12 6 270 1 9 320 845 611 1 12 400 1
Patient 17 (age 23) has multiple emergency room visits prior to
treatment. On day 30 of treatment, Patient 11 walked in and
announced, "I am cured." Patient 11's age and size matched a mean
peak flow of 590.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 280
477 161 4 30 770 301 98 0 44 750 0
Patient 18 (age 45) has been in the intensive care unit three times
for asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 370
141 3 7 420 1
Patient 19 (age 24) had made nearly two hundred emergency room
visits for asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 280
447 5 8 460 4
Patient 20 (age 25) had been in the emergency room twice and the
intensive care unit once for asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 310
128 108 3 14 500 2
Patient 21 (age 21)
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 440
341 115 2 7 530 1 14 540 0
Patient 22 (age 38) had five emergency room visits for asthma prior
to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 250
246 285 2 27 480 1
Patient 23 (age 23) had been in the emergency room twice and the
intensive care unit once for asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 380
3350 5 3 470 3 6 530 1
Patient 24 (age 36) had been hospitalized twice and in the
intensive care unit once for asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 280
186 501 2 7 500 1 14 620 405 555 0
Patient 25 (age 18) had made an emergency room visit for asthma
prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 450
2 8 660 1
Patient 26 (age 27) had made three emergency room visits for asthma
prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 270
192 220 4 7 430 2
Patient 27 (age 32)
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 550
4 7 590 282 230 2 14 780 565 202 0 25 760 0
Patient 28 (age 48) had made five emergency room visits and been in
the intensive care unit three times for asthma prior to
treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 230
154 1 8 290 0
Patient 29 (age 28) had multiple hospitalizations for asthma prior
to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 460
2 7 500 1
Patient 30 (age 28)
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 420
114 18 4 7 550 3 14 550 3 21 560 13 2
Patient 31 (age 21) had been in the emergency room nearly fifty
times and hospitalized nearly eighty times for asthma prior to
treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 350
352 104 4 16 610 200 2
Patient 32 (age 21) had been in the emergency room five times and
hospitalized ten times for asthma prior to treatment.
Peak IgE Inhaler use Day Flow Eosinophils antibodies per day 1 380
202 39 4 14 540 0
* * * * *